The volatile anesthetics (halothane, enflurane & isoflurance) depress myocardial contractility by differing mechanisms. Halothane causes equal depression at all stimulation frequencies, and depresses slow inward (calcium) current (Isi) based on slow action potential experiments. Equi-anesthetic concentrations of isoflurane depress tension much less at high frequencies, and causes little depression of Isi. Enflurane appears to have intermediate effects. This study will complete the voltage clamp investigation on anesthetic effects on myocardial ionic currents employing the single sucrose gap technique on ferret muscle, and clarify the differences among the anesthetics. The minimal effects of isoflurane on Isi, and the depressant effects of isoflurane which are similar to those of dantrolene sodium (which inhibits sarcoplasmic reticulum (SR) release of Ca in skeletal muscle) suggest that effects upon myocardial excitation-contraction (E-C) coupling are mediated by changes in the intracellular Ca+2 (Ca) stores. Therefore, anesthetic effects upon transsarcolemmal and intracellular Ca fluxes which activate contraction (activator Ca) will be assessed using radio-isotope fluxes. In guinea pig ventricle, anesthetic effects on Ca uptake into the myocardium (stimulated and at rest) will be studied with Ca45 (and Mn+2), and can be compared with electrophysiologic measurements, which predict greater inhibition of uptake by halothane. The efflux of Ca45 can be used to measure anesthetic effects on the quantity and mobilization of Ca from "superficial" and internal (SR) pools which contribute to contractile activation. These effects on Ca fluxes can then be compared with the those of Ca entry blockers and dantrolene, providing further insight into the mechanisms and potential interactions. The E-C coupling of rat and frog greatley differ, in that the rat has very large internal (SR) activator Ca stores, while in the frog, activator Ca arises primarily from outside the cell. Therefore, these tissues will be studied for differential anesthetic depression. Myocardial ischemia causes derangements in intracellular Ca which are thought to mediate in part the accompanying dysrhythmias and cell death. Study of alterations in Ca fluxes caused by anesthetics will be of value in defining their actions in patients with myocardial ischemia and in other settings of altered Ca metabolism such as following cardioplegia. Potential anesthetic interaction with Ca entry blockers in depleting myocardial activator Ca will also be elucidated.